Schizophrenia and bipolar disorder (BD) share elements that can sometimes be difficult to distinguish. Both are characterized by psychosis, but in schizophrenia, auditory hallucinations are more common, whereas in BD, grandiosity and excitement are more prevalent. While paranoia can be present in both conditions, it is more systematic in schizophrenia. Moreover, negative symptoms and cognitive dysfunction are core psychopathologies of schizophrenia, in contrast to BD, in which mood lability and affective cycling dominate.1 These distinctions are crucial because early differential diagnosis is important for appropriate treatment.2,3

Two classifications have been used for schizophrenia and BD. The categorical classification regards BD and schizophrenia as distinct diagnoses. It was Emil Kraepelin4 who played an important role in differentiating these disorders. Kraepelin considered “manic depression” as an episodic illness with periods of functional recovery and dementia praecox as a degenerative persistent condition, leading to poor outcome, with negative symptoms as the primary characteristics.2

Eugen Bleuler expanded the psychological characteristics of schizophrenia to include disorganization in thought processes, but recognized affective features as existing along a continuum. Recent research suggests that schizophrenia and BD psychosis may be two ends of a continuum rather than discrete diagnostic entities, with overlap and blurred boundaries.2

The presence of affective components in schizophrenia suggests the existence of an entity called schizoaffective disorder — a diagnosis with some controversy because it is possible that “schizoaffective disorders” are merely affective disorders with psychotic features.5 Indeed, one study compared data from outpatients with a diagnosis of schizophrenia or schizoaffective disorder with that of control participants not undergoing psychiatric treatment and found that schizophrenia and schizoaffective disorder were “largely indistinguishable on key cognitive, social cognitive and neural measures.”6

Shared and Differing Vulnerabilities

There have been multiple lines of research comparing psychosis in schizophrenia with psychosis in BD and other affective disorders.  For example, evidence from family, high-risk, and twin studies suggest both shared and specific vulnerabilities to schizophrenia and affective psychosis.7

Some studies have pointed to similarities in neuropathology between the two disorders,7,8 while other research has suggested that the neural underpinnings differ. For example, researchers reviewed magnetic resonance imaging data and found greater gray matter volume deficits in the right cingulate and the superior temporal and calcarine cortices in people with BD compared with healthy participants. Patients with schizophrenia showed deficits in widespread cortical and subcortical areas when compared with the control group and greater deficits in the insula and thalamus when compared with patients with BD.9

Genetically, there appear to be differing and common genomic regions implicated in schizophrenia and BD,10 or a “gradient of polygenic liability across [schizophrenia] and [BD], indexed by the occurrence of psychosis and level of mood incongruence.”11 For example, genomic regions implicated in schizophrenia include 6p24–22, 1q21–22, 13q32–34, 8p21–22, 6q16–25, 22q11–12, 5q21–q33, 10p15–p11, and 1q42. By contrast, genetic regions of interest in BD include 6q16–q22, 12q23–q24, and regions of 9p22–p21, 10q21–q22, 14q24–q32, 13q32–q34, 22q11–q22, and chromosome 18.10 Specific genes or loci common to both disorders include DAOA(G72), DISC1, and NRG1.10

Inflammation may be implicated in both schizophrenia and BD. A meta-analysis of studies of schizophrenia, BD, and unipolar major depression (68 studies of acute illness and 46 studies of chronic illness) found levels of 2 cytokines (interleukin-6 [IL-6]; tumor necrosis factor-α [TNF-α]), one soluble cytokine receptor (sIL-2R), and one cytokine receptor antagonist (IL-1RA) to be significantly increased in acutely ill patients with schizophrenia, bipolar mania, and major depression compared with controls (P < 0.01). However, response to treatment of these inflammatory cytokines yielded differences between the 3 disorders, with a significant decrease in IL-6 levels in both schizophrenia and major depression (P < 0.01), an increase in sIL-2R levels in schizophrenia, and a decrease in IL-1RA levels in bipolar mania.12

Developmental risk factors (eg, prenatal maternal nutritional deficiency, season of birth, urbanicity, and obstetric complications) have been found in both schizophrenia and BD, with most studies indicating a gradient of severity with a smaller effect size in BD in comparison with schizophrenia.7

In conclusion, it appears that “a simple binary classification of these disorders represents an oversimplification and it may be more apposite to think in terms of genetic influences on six continuous symptom dimensions: neurobiological, cognitive, positive, negative, depressive and manic symptoms.”7 Indeed, schizophrenia and BD might be seen as a single “spectrum disorder,” akin to autism.13

First-Person Accounts

Listening to patients’ narratives can help improve the quality of psychosis care.14 To that end, Psychiatry Advisor interviewed individuals who were willing to share their stories.

Elyn Saks, JD, PhD, is the Orrin B Evans Distinguished Professor of Law, Psychology, and Psychiatry and the Behavioral Sciences at the University of Southern California Gould Law School. Dr Saks is also the author of The Center Cannot Hold: My Journey Through Madness,15 a memoir of her life as a person with schizophrenia.

For me, schizophrenia is basically like a waking nightmare, with bizarre images and impossible things happening. In an actual nightmare, you sit up in bed and all of the frightening distortions that appear in dreams vanish. But when you have a psychotic episode, that doesn’t happen. I have had delusions in which I’ve killed hundreds of thousands of people or have hallucinated a person with a raised knife standing at the foot of my bed.

My first frank episode of acute psychosis took place when I was around 16, and I suddenly started walking home from school in the middle of the day. I began to feel the houses were getting weird and sending me messages: “You are special. You are especially bad. Now walk. Cries and whispers.” In contrast to people with BD, whose psychosis often makes them feel special in a grandiose way, my “specialness” — and I understand that this is not uncommon in people with schizophrenia — was consistently negative. I was worse than everyone else.

After college, I went to Oxford University and experienced 2 years of negative symptoms. I had difficulty working and had no friends. But I had the good fortune of being able to get into psychoanalytic treatment. There were times when I went to sessions, even in a state of psychosis. Being in analysis interrupted the negative symptoms.

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During the seventh week of my first year of Yale Law School, after my return from Oxford, I experienced acute psychosis and I was forced to withdraw from law school for the remainder of the year and was hospitalized for 5 months. I also experienced disorganized speech and thoughts, as well as paranoia. It was brought to the attention of my professor when I was in the Yale law library and told my friends that the words in the case we were studying were jumping around the page. “I think someone’s infiltrated my copies of the case. We’ve got to case the joints. I don’t believe in joints, but they do hold your body together.”

When I reflect on my journey, I acknowledge the role of psychoanalysis as well as medication and the support of friends and family in my recovery. Many people think that psychoanalysis and similar approaches are not helpful for people with schizophrenia but I know that it was very important for me. Developing a relationship with the analyst spread to the rest of my life, giving me skills to make friends and develop relationships. Of course, medication played an essential role in my recovery as well. I am grateful to have found a regimen that has kept psychosis largely at bay.

I always encourage psychiatrists, psychologists, and other professionals not to have preconceptions or lower their expectations when they work with people with schizophrenia. Make your default approach that people can be helped to live up to their pre-illness potential and to be high-functioning members of society, with fulfilling employment and relationships.

Marc S Atkins, PhD, is Professor of Psychiatry and Psychology and Director of the Institute for Juvenile Research, University of Illinois at Chicago. He is also Director of the Community Based Dissemination and Implementation Science Center for Clinical Translational Science. He is a contributor to Breaking the Silence: Mental Health Professionals Disclose Their Personal and Family Experiences of Mental Illness.16

My psychotic episode took place during the Vietnam War, when I was involved in anti-war activism. Beyond the angst of being a 19-year-old away from home at college, I was going through a very difficult, intense, and scary time in my life. I was riddled with anxiety, some of it justified — my friends were being indicted for inciting a riot on campus and I was subpoenaed to testify.

I experienced racing thoughts, anxiety, insomnia, and difficulty concentrating. I was with a friend and I heard someone call my name. When my friend didn’t hear anything, I became even more frightened that I was hearing voices.

I had gone home for the summer and had taken classes, so I wasn’t entirely dysfunctional. But when I returned, the intensity of being back, being subpoenaed, and hearing a voice left me feeling terrified and defeated and I went back home. My parents sent me to a therapist whom I didn’t want to see. I stopped after a few sessions, but after I returned home in midsemester, I found therapy helpful. This is one message I would like to get across to readers who are therapists — always keep the door open to clients who leave therapy because you never know when they might want to come back. And as a patient, I know that just because therapy didn’t work out once doesn’t mean it won’t work the next time.

I would also like to emphasize that there is no substitute, including therapy, for the support of family and friends. There is nothing more important we can do as professionals than to help people reconnect to family and friends. I am fortunate to have had a supportive family and group of friends, who helped me through my recovery and enabled me to return to college and continue my life and my studies.

John A. Emery, MD, is a retired urologist who served as a navy doctor with the US Marine Corps during the Vietnam War. He is the author of A Surgeon’s Life with Bipolar Disorder17 and US Medical Care and Related Factors in the Vietnam War.18 He currently resides in Merced, California.

I went to medical school at the UCSF and during the Vietnam War, I was in the Marine Corps as a physician. When I returned, I did a urology residency and began to practice medicine. Out of the blue, I experienced a devastating depression that lasted for 5 years, accompanied by flashbacks of the Vietnam War.

The depression was followed by a period of hyperactivity, in which I experienced elation, rapid speech, and a sense of strength and athletic prowess. I thought we could start a new medical program in the hospital, which was impractical at the time. I also was working on a new procedure in medicine, which at the time wasn’t well proven but ultimately worked out to be an effective procedure. This is what led me to seek treatment. I saw a bipolar specialist and was diagnosed with BD. After this, I took a year off, studied the disease, and also participated in a support group program. When the year ended and I had stabilized, I began practicing again.

Since then, I’ve had 3 major episodes of hyperactivity and 3 of depression. I continued to work closely with my physicians and learned to listen to my body and mood. If I felt that I was becoming manic or depressed in a severe way, I took time off from my practice until I had stabilized. No patient has ever experienced a negative outcome because of my disease. [However], I recall how dramatic, severe, devastating, and terrifying the episodes — both manic and depressive — were.

Ella Barstein, LCSW, is the pseudonym of a New Jersey-based therapist in private practice. She requested to be anonymous for this article.

I have bipolar disorder II, but did not realize it for many years. In retrospect, I can identify a manic episode I had in college. For several weeks, I was working on a paper. I remember not sleeping, having racing thoughts, and believing that my paper was going to change the entire field. I remember visiting my professor’s house and speaking very rapidly and inappropriately at the dinner table. I felt euphoria and a sense of invincibility. When my paper was submitted, my professor thought it was “adequate” but certainly not the tour de force I imagined it to be, so I crashed into a serious depression that lasted for a few months and eventually lifted when I met a man I later married.

After I began clinical practice, I realized I had BD. I consulted a psychiatrist who wanted me to begin mood stabilizing medication, which I resisted until I became so depressed that I had constant suicidal ideation. I started taking gabapentin as a mood stabilizer and then lamotrigine was added and I stabilized.

I never entered frank psychosis, but I have a client with BD I whose story I will tell, altering some details to protect his privacy. My client experienced a manic episode in which he was convinced he was writing the Great American Novel. His behavior was similar to mine during my period of mania, but he showed signs of psychosis even beyond his delusion of grandeur. He became convinced that family members were going to steal the plot of his novel and that he required “protection” from their intrusions into his thoughts. He believed that using round items (eg, eating bagels instead of square slices of bread) would create a “circle of protection.”

When the novel was rejected by publishers, he became depressed and refused to leave his room. He was hospitalized when he began displaying violence toward family members, who, he believed, had sabotaged his literary success. Treatment was initiated with olanzapine, lithium, and lamotrigine and his psychosis subsided, although his depression continued for months and has still not abated. When he was discharged from the hospital, he participated in an outpatient day program that offers cognitive behavioral therapy and psychoeducation. He appears to be regaining functionality, despite his ongoing depression. I am hopeful that insight into his illness and commitment to his medication regimen will be assets in his journey toward recovery.

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